Mild Nonalcoholic Fatty Liver Disease Research Articles

Angiopoietin-like protein 8/betatrophin correlates with hepatocellular lipid content independent of insulin resistance in non-alcoholic fatty liver disease patients.

Aims/IntroductionTo explore angiopoietin‐like protein 8 (ANGPTL‐8) levels, and its association with hepatocellular lipid content (HCL) and insulin resistance in patients with different extents of non‐alcoholic fatty liver disease (NAFLD).Materials and MethodsIn 48 adults were recruited, of which 12 had no NAFLD (HCL < 5.5%; group 1), 18 had mild NAFLD (5.5% ≤ HCL < 10.0%; group 2) and 18 had moderate‐to‐severe NAFLD (HCL ≥ 10.0%; group 3). The peripheral insulin sensitivity of all participants was monitored by a hyperinsulinemic‐euglycemic clamp (M value), as well as the magnetic resonance image of HCL. Serum ANGPTL‐8, blood glucose levels and lipid profiles were also recorded in the study.ResultsGroup 3 had a worse metabolic profile, and had the highest ANGPTL‐8 level (1,129 ± 351 pg/mL vs 742 ± 252 pg/mL, 765 ± 301 pg/mL, P = 0.001) compared with those in group 1 and group 2. In all metabolic profiles, HCL positively correlated the strongest with ANGPTL‐8 (r = 0.436, P = 0.042). Multivariate stepwise linear regression analysis showed ANGPTL‐8 and alanine aminotransferase were independent determinants of HCL (P = 0.002, P < 0.001, respectively), and these two indexes explained 67.4% of the variation of HCL (P < 0.001).Conclusions ANGPTL‐8 was positively correlated with hepatocellular lipid content independent of obesity and insulin resistance, indicating that ANGPTL‐8 might be a new and important important predictor of the severity of NAFLD.

Identification of the genomic region under epigenetic regulation during non-alcoholic fatty liver disease progression.

The progression of non-alcoholic fatty liver disease (NAFLD) is affected by epigenetics. We undertook co-methylation and differentially methylated region (DMR) analyses to identify the genomic region that is under epigenetic regulation during NAFLD progression. We collected liver biopsy specimens from 60 Japanese patients with NAFLD and classified these into mild (fibrosis stages 0-2) or advanced (fibrosis stages 3-4) NAFLD. We carried out a genome-wide DNA methylation analysis and identified the differentially methylated CpGs between mild and advanced NAFLD. Differentially methylated regions with multiple consecutive differentially methylated CpGs between mild and advanced NAFLD were extracted. Co-methylation analysis showed that individual differentially methylated CpG sites were clustered into three modules. The CpG sites clustered in one module were hypomethylated in advanced NAFLD and their annotated genes were enriched for "immune system" function. The CpG sites in another module were hypermethylated and their annotated genes were enriched for "mitochondria" or "lipid particle", and "lipid metabolism" or "oxidoreductase activity". Hypomethylated DMRs included tumorigenesis-related genes (FGFR2, PTGFRN, and ZBTB38), the expressions of which are upregulated in advanced NAFLD. Tumor suppressor MGMT had two DMRs and was downregulated. Conversely, FBLIM1 and CYR61, encoding proteins that reduce cell proliferation, showed hypomethylated DMRs and were upregulated. Expression of the antioxidant gene NQO1 was upregulated, with a hypomethylated DMR. The DMR containing cancer-related MIR21 was hypomethylated in advanced NAFLD. Co-methylation and DMR analyses suggest that the NAFLD liver undergoes mitochondrial dysfunction, decreased lipid metabolism, and impaired oxidoreductase activity, and acquires tumorigenic potential at the epigenetic level.

Serum fetuin A level is associated with nonalcoholic fatty liver disease in Chinese population.

ObjectiveTo investigate the association between serum fetuin A concentration and non-alcoholic fatty liver disease (NAFLD) in Chinese population.MethodsThis case-control study enrolled 79 NAFLD cases and 79 non-NAFLD controls. All subjects were selected from Chinese population who received annual health examination in the First Affiliated Hospital of Zhejiang University in 2016. NAFLD was diagnosed mainly based on abdominal ultrasonography. The severity of NAFLD was categorized by serum level of alanine aminotransferase. Serum fetuin A was measured by ELISA.ResultsSerum fetuin A level in NAFLD patients was significantly lower than that in controls (0.27±0.17 vs. 0.32±0.12g/L, P < 0.05). Compared with controls, mild NAFLD (0.24±0.16 g/L, P < 0.05) and moderate NAFLD (0.25±0.17 g/L, P < 0.05) had significantly lower concentration of Fetuin A, while Fetuin A level tended to slightly increase with the severity of NAFLD. The prevalence rate of NAFLD decreased (75 %, 40 %, and 36 %), as Fetuin A level elevated. ROC curve of Fetuin A was developed to predict the presence of NAFLD. Area under ROC was 0.656.ConclusionSerum level of Fetuin A was lower in NAFLD patients than controls, while Fetuin A level increased with the severity of NAFLD, indicating a potential predicting role of Fetuin A in the development of NAFLD.

Candidate genes investigation for severe nonalcoholic fatty liver disease based on bioinformatics analysis.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide. However, its etiology and fundamental pathophysiology for the disease process are poorly understood. In this study, we thus used bioinformatics to identify candidate genes potentially causative of severe NAFLD. Gene expression profile data GSE49541 were downloaded from the Gene Expression Omnibus database. Tissues samples from 32 severe and 40 mild NAFLD patients were evaluated to identify differentially expressed genes (DEGs) between the 2 groups, followed by analyses of Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes pathways. Then, a weighted protein-protein interaction (PPI) network was constructed, and subnetworks and candidate genes were screened. Moreover, the GSE48452 data (14 normal liver tissue samples and 18 nonalcoholic steatohepatitis samples) were used to verify the results obtained from the above analyses. A total of 100 upregulated genes and 24 downregulated ones were identified in severe NAFLD. Functional enrichment and pathway analyses showed that these DEGs were mainly associated with cell adhesion, inflammatory response, and chemokine activity. The top 5 subnetworks were selected based on the PPI network. A total of 5 hub genes, including ubiquilin 4 (UBQLN4), amyloid-beta precursor protein (APP), sex hormone-binding globulin (SHBG), cadherin-associated protein beta 1 (CTNNB1) and collagen type I alpha 1 (COL1A1), were considered to be candidate genes for NAFLD. In addition, the verification data confirmed the status of COL1A1, SHBG, and APP as candidate genes. UBQLN4, APP, CTNNB1, SHBG, and COL1A1 might be involved in the development of NAFLD, and are proposed as the potential markers for predicting the development of this condition.

Lipid profile in different grades of Ultrasonic Non-Alcoholic Fatty Liver Disease

Background &amp; Objectives: This study was conducted with objective of studying the lipid abnormalities in patients with non-alcoholic fatty liver disease diagnosed on the basis of ultrasound.Materials &amp; Methods: Total 100 patients consisting of 67 males and 37 females diagnosed as Non-alcoholic fatty liver disease on the basis of ultrasound were included in the study. Laboratory values of different lipid parameters were compared in different grades of these patients.Results: Out of total 100 cases, mild nonalcoholic fatty liver disease was found in 83 %, moderate in 17 % and severe in none of the participants. Age of the participants ranged from 26 to 79 years with mean being 45 ± 11.99 years. Presence of dyslipidemia was found in 94 % of the cases. Triglycerides, total cholesterol and low density lipoprotein levels were raised in 59, 53, 72% of the cases respectively and High density lipoprotein level was decreased in 57% of participants. There was significant positive correlation of presence of non-alcoholic fatty liver disease with increasing levels of serum total cholesterol (P value &lt;0.001), low density lipoprotein (P value &lt;0.001) and triglyceride (P value &lt;0.001) and significantly decreasing high density lipoprotein (P value &lt;0.001). Whereas increasing grades of non-alcoholic fatty liver disease weren’t significantly associated with increasing level of lipid abnormalities.Conclusion: This study showed the high prevalence of dyslipidemia in non-alcoholic fatty liver patients. Early detection with simple non-invasive ultrasonography is very useful to detect dyslipidemic patients.

Evaluation of Biomarkers in Egyptian Patients with Different Grades of Nonalcoholic Fatty Liver Disease.

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is a silent disease; its spectrum includes simple steatosis, nonalcoholic steatohepatitis and fibrosis. Pro- and anti-inflammatory cytokines play roles in the pathogenesis of NAFLD and insulin resistance (IR). Moreover, plasma cell antigen-1 (PC-1) is related to IR and associated with NAFLD progression. Therefore, we aimed to detect biomarkers, ultrasonographic and anthropometric findings capable of differentiating NAFLD grades, since most previous investigators were concerned more with NAFLD patients without classifying them into grades.Methods: A total of 87 NAFLD patients (31 with grade 1 (mild NAFLD), 26 with grade 2 (moderate NAFLD) and 30 with grade 3 (severe NAFLD) were included in the study, in addition to 47 controls (grade 0). All subjects underwent ultrasonographic examination for NAFLD diagnosis. Serum interleukin-10 (IL-10), plasma interleukin-18 (IL-18) and plasma PC-1 levels were determined using enzyme-linked immunosorbent assay.Results: Homoeostasis model assessment (HOMA)-IR was higher in different NAFLD grades than in controls. Ultrasonographic and anthropometric findings and lipid profile indices (except for high-density lipoprotein cholesterol, which was decreased) were increased with NAFLD progression. Grade 3 patients showed significant increase in levels of IL-18 and significant decrease in IL-10 and PC-1 levels when compared to grade 1 patients.Conclusion: Anthropometric and ultrasonographic findings were valuable in differentiating NAFLD grades. IR is very important in NAFLD pathogenesis. IL-18, HOMA-index and PC-1 levels could be used to differentiate between NAFLD grades, together with other measurements.

Identification of core gene networks and hub genes associated with progression of non-alcoholic fatty liver disease by RNA sequencing.

Non-alcoholic fatty liver disease (NAFLD) progresses because of the interaction between numerous genes. Thus, we carried out a weighted gene coexpression network analysis to identify core gene networks and key genes associated with NAFLD progression. We enrolled 39 patients with mild NAFLD (fibrosis stages 0-2) and 21 with advanced NAFLD (fibrosis stages 3-4). Total RNA was extracted from frozen liver biopsies, and sequenced to capture a large dynamic range of expression levels. A total of 1777 genes differentially expressed between mild and advanced NAFLD (q-value <0.05) clustered into four modules. One module was enriched for genes that encode cell surface or extracellular matrix proteins, and are involved in cell adhesion, proliferation, and signaling. This module formed a scale-free network containing four hub genes (PAPLN, LBH, DPYSL3, and JAG1) overexpressed in advanced NAFLD. PAPLN is a component of the extracellular matrix, LBH and DPYSL3 are reported to be tumor suppressors, and JAG1 is tumorigenic. Another module formed a random network, and was enriched for genes that accumulate in the mitochondria. These genes were downregulated in advanced NAFLD, reflecting impaired mitochondrial function. However, the other two modules did not form unambiguous networks. KEGG analysis indicated that 71 differentially expressed genes were involved in "pathways in cancer". Strikingly, expression of half of all differentially expressed genes was inversely correlated with methylation of CpG sites (q-value <0.05). Among clinical parameters, serum type IV collagen 7s was most strongly associated with the epigenetic status in NAFLD. Newly identified core gene networks suggest that the NAFLD liver undergoes mitochondrial dysfunction and fibrosis, and acquires tumorigenic potential epigenetically. Our data provide novel insights into the pathology and etiology of NAFLD progression, and identify potential targets for diagnosis and treatment.

Low Serum Sex Hormone-Binding Globulin Associated with Insulin Resistance in Men with Nonalcoholic Fatty Liver Disease.

The presence of nonalcoholic fatty liver disease (NAFLD) is a strong risk predictor for type 2 diabetes (T2D). A reduction in sex hormone-binding globulin (SHBG) is associated with NAFLD. Low SHBG is also associated with insulin resistance (IR). However, very limited data are available for the association of SHBG and IR in patients with NAFLD. The study aims to clarify the association between SHBG and IR in patients with NAFLD. In this cross-sectional study, 334 men with NAFLD were recruited. SHBG, total testosterone, free testosterone, total cholesterol, triglyceride, insulin, and glucose concentrations were measured. Homeostatic model assessment (HOMA)-IR and HOMA-β were calculated. Spearman's correlations and multiple linear regressions were used to analyze the association between SHBG and IR. Men with moderate-severe NAFLD had higher waist circumference, BMI, total cholesterol, triglyceride, insulin, HOMA-IR, HOMA-β, and free testosterone, but lower SHBG than the mild NAFLD. The moderate-severe NAFLD group exhibited higher HOMA-IR (2.38±1.35 vs. 4.16±2.84, p<0.001) and lower SHBG (25.89±11.89 vs. 30.13±12.97 nmol/l, p<0.001) than the other group. SHBG value was negatively correlated with insulin, and HOMA-IR, but was not significantly correlated with glucose and testosterone. The multiple linear regression analysis showed that SHBG was significantly associated with insulin (β=- 0.241, p<0.001), and HOMA-IR (β=- 0.229, p<0.001), even adjusting for potential confounders. In conclusion, low serum SHBG is associated with IR in men with NAFLD.

Altered microRNA-9 Expression Level is Directly Correlated with Pathogenesis of Nonalcoholic Fatty Liver Disease by Targeting Onecut2 and SIRT1.

BackgroundMicroRNA-9 (miR-9) was detected in nonalcoholic fatty liver disease (NAFLD) patients to understand the role of miR-9 in NAFLD development.Material/MethodsBetween February 2014 and February 2015, 105 cases of NAFLD were recruited and confirmed by liver biopsy pathology, including patients with mild NAFLD (n=58) and moderate-severe NAFLD (n=47); nonalcoholic steatohepatitis (NASH) (n=53) and non-NASH (n=52); and 50 healthy participants were regarded as the healthy control group. MiR-9 expression was measured by qRT-PCR. For in vitro experiments, L-02 normal liver cells were divided into normal control group (cultured with original culture medium), dimethyl sulfoxide (DMSO) group (cultured with DMSO) and oleic acid group (cultured with oleic acid to induce fatty change), and MTT assay was used to measure the effect of different oleic acid concentrations on cell proliferation. Nile red staining was used to detect intracellular accumulation of lipid droplets. Further, synthetic miR-9 mimic and its control and miR-9 inhibitors and its control were independently transfected into L-02 cells.ResultsMiR-9 levels in the mild NAFLD group and moderate-severe NAFLD group were significantly higher than in the healthy control group (both P<0.05). Mean fluorescence intensity of lipid droplets increased with the duration of induction, and were dramatically higher in oleate-treated L-02 cells; intracellular triglyceride (TG) content was also higher. miR-9 levels significantly increased following oleate induction. Importantly, miR-9 levels were significantly elevated upon miR-9 mimic transfection. Conversely, miR-9 level was lowered with miR-9 inhibitors transfection. Additionally, Onecut2 and SIRT1 were identified as miR-9 targets.ConclusionsA positive relationship between miR-9 and steatosis was established with our results that miR-9 mimic transfection decreased intracellular lipid content. Finally, we identified 2 miR-9 targets, Onecut2 and SIRT1, which may be crucial players in NAFLD development.

Fibroblast growth factor 21 reflects liver fat accumulation and dysregulation of signalling pathways in the liver of C57BL/6J mice

Fibroblast growth factor 21 (Fgf21) has emerged as a potential plasma marker to diagnose non-alcoholic fatty liver disease (NAFLD). To study the molecular processes underlying the association of plasma Fgf21 with NAFLD, we explored the liver transcriptome data of a mild NAFLD model of aging C57BL/6J mice at 12, 24, and 28 months of age. The plasma Fgf21 level significantly correlated with intrahepatic triglyceride content. At the molecular level, elevated plasma Fgf21 levels were associated with dysregulated metabolic and cancer-related pathways. The up-regulated Fgf21 levels in NAFLD were implied to be a protective response against the NAFLD-induced adverse effects, e.g. lipotoxicity, oxidative stress and endoplasmic reticulum stress. An in vivo PPARα challenge demonstrated the dysregulation of PPARα signalling in the presence of NAFLD, which resulted in a stochastically increasing hepatic expression of Fgf21. Notably, elevated plasma Fgf21 was associated with declining expression of Klb, Fgf21’s crucial co-receptor, which suggests a resistance to Fgf21. Therefore, although liver fat accumulation is a benign stage of NAFLD, the elevated plasma Fgf21 likely indicated vulnerability to metabolic stressors that may contribute towards progression to end-stage NAFLD. In conclusion, plasma levels of Fgf21 reflect liver fat accumulation and dysregulation of metabolic pathways in the liver.

Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades.

Hepatic steatosis is characterised by excessive triglyceride accumulation in the form of lipid droplets (LD); however, mechanisms differ in drug induced (DIS) and/or non-alcoholic fatty liver disease (NAFLD). Here we hypothesized distinct molecular circuits of microRNA/LD-associated target genes and searched for mechanistically linked serum and tissue biomarkers that would distinguish between DIS and human NAFLD of different grades. We analysed >800 rat hepatic whole genome data for 17 steatotic drugs and identified 157 distinct miRNAs targeting 77 DIS regulated genes. Subsequently, genomic data of N = 105 cases of human NAFLD and N = 32 healthy controls were compared to serum miRNA profiles of N = 167 NAFLD patients. This revealed N = 195 tissue-specific miRNAs being mechanistically linked to LD-coding genes and 24 and 9 miRNAs were commonly regulated in serum and tissue of advanced and mild NAFLD, respectively. The NASH serum regulated miRNAs informed on hepatic inflammation, adipocytokine and insulin signalling, ER-and caveolae associated activities and altered glycerolipid metabolism. Conversely, serum miRNAs associated with blunt steatosis specifically highlighted activity of FOXO1&HNF4α on CPT2, the lipid droplet and ER-lipid-raft associated PLIN3 and Erlin1. Altogether, serum miRNAs informed on the molecular pathophysiology of NAFLD and permitted differentiation between DIS and NAFLD of different grades.

SERUM 25‐HYDROXY D3 LEVELS IN NONALCOHOLIC FATTY LIVER DISEASE

BackgroundIt has become the most common liver disease in the world. Nonalcoholic fatty liver disease (NAFLD) is a wide range of disorders from a simple steatosis to fibrosis/cirrhosis. Although some studies show association between vitamin D and NAFLD; studies showing the association in different severity of NAFLD are limited.AimThe aim of this study to evaluate serum 25‐hydroxy vitamin D 3 levels in different severity of NAFLD.Materials and MethodsFifty three morbidly obese subjects (BMI ≥40 kg/m2) were included into the study. NAFLD activity scores (NAS) were calculated according to liver biopsies and subjects were divided into 3 group; mild NAFLD (n =15, NAS score: ≤2), moderate NAFLD (n =23, NAS score: 3–4), severe NAFLD (n =15, NAS score: ≥5). Blood samples were collected. Liquid chromatography/tandem mass spectrometry was used to analyze the serum vitamin D levels.ResultsSerum 25‐Hydroxy vitamin D 3 levels were significantly lower in moderate and severe NAFLD groups (25.9 ± 9.10 ng/ml and 21.9 ± 7.14 ng/ml, respectively) than the mild NAFLD group (34.5 ± 10.19 ng/ml). Total cholesterol and HDL cholesterol levels were lower in severe NAFLD group (165.0 ± 38.64 mg/dl and 39.8 ±8.33 mg/dl). Furthermore, serum folic acid levels were significantly lower in moderate and severe NAFLD groups (13.8 ± 4.00 nmol/L and 14.9 ± 4.38 nmol/L, respectively) than mild NAFLD group (17.9 ± 3.98 nmol/L). Serum 25‐ Hydroxy D 3 levels and NAS were not significantly different between gender groups. Serum vitamin D levels showed an inverse correlation with NAS (r = −0.332, p &lt; 0.05). NAS levels did not show any significant difference between gender groups.ConclusionSerum 25‐Hydroxy vitamin D 3 levels may differ in different severity of NAFLD.

Hepatic enzyme concentrations as indicators of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has emerged as a world-wide problem because it runs an asymptomatic course, ultimately leading to cirrhosis of the liver and portal hypertension, resulting in death. The prevalence of the disease accounts for 3-24% of the population in several countries. Generally there are increased concentrations of hepatic enzymes as markers of liver damage, such as serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and gamma glutamyl transferase (GGT). The aim of the present study was to determine the concentrations of hepatic enzymes as markers of NAFLD. The study design was cross-sectional, involving 90 subjects meeting the inclusion and exclusion criteria. The degree of severity NAFLD was determined by ultrasonography and the concentrations of SGOT, SGPT and GGT by automated clinical chemistry analyzer. The results indicated that there were 32 subjects with mild NAFLD (35.6%), 35 subjects with moderate NAFLD (38.9%) and 23 subjects with severe NAFLD (25.6%). There was a significant difference in degree of NAFLD by gender (p&lt;0.05), where severe NAFLD was more frequent in males than in females. Concentrations of SGOT, SGPT and GGT were significantly different between degrees of NAFLD (p&lt;0.05). The conclusion is that SGOT, SGPT and GGT concentrations are indicators of degree of NAFLD.

Systematic transcriptome analysis reveals elevated expression of alcohol‐metabolizing genes in NAFLD livers

Obese animals and non-alcoholic fatty liver disease (NAFLD) patients exhibit elevated blood alcohol, suggesting potential contributions of alcohol metabolism to the development of NAFLD. Liver gene expression in patients with biopsy-proven mild (N = 40) and severe (N = 32) NAFLD were compared to that in healthy liver donors (N = 7) and alcoholic hepatitis (AH; N = 15) using microarrays. Principal components analyses (PCA) revealed similar gene expression patterns between mild and severe NAFLD which clustered with those of AH but were distinct from those of healthy livers. Differential gene expression between NAFLD and healthy livers was consistent with established NAFLD-associated genes and NAFLD pathophysiology. Alcohol-metabolizing enzymes including ADH, ALDH, CYP2E1, and CAT were up-regulated in NAFLD livers. The expression level of alcohol-metabolizing genes in severe NAFLD was similar to that in AH. The NAFLD gene expression profiles provide new directions for future investigations to identify disease markers and targets for prevention and treatment, as well as to foster our understanding of NAFLD pathogenesis and pathophysiology. Particularly, increased expression of alcohol-metabolizing genes in NAFLD livers supports a role for endogenous alcohol metabolism in NAFLD pathology and provides further support for gut microbiome therapy in NAFLD management. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley © Sons, Ltd.

Combined Association of Vitamin D and Sex Hormone Binding Globulin With Nonalcoholic Fatty Liver Disease in Men and Postmenopausal Women: A Cross-Sectional Study.

This study aimed to explore the combined associations of 25(OH)-vitamin D and sex hormone binding globulin (SHBG) with nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women. Our data, which were based on the population, were collected from 16 sites in East China in 2014. There were 2700 men with a mean age of 53 years and 1461 women over 55 who were considered postmenopausal enrolled in the study. Levels of 25(OH)D and SHBG were measured using chemiluminescence assay. NAFLD was measured using liver ultrasound. Multivariable-adjusted logistic regression models examined associations of 25(OH)D and SHBG tertiles with odds of mild and moderate-severe NAFLD. Both the low 25(OH)D and low SHBG groups were significantly associated with higher odds of mild NAFLD (men: OR 1.37, 95% CI 1.05, 1.78 in low 25(OH)D group; OR 1.73, 95% CI 1.23, 2.45 in low SHBG group; women: OR 1.51, 95% CI 1.08, 2.12 in low 25(OH)D group; OR 2.16, 95% CI 1.48, 3.14 in low SHBG group) and moderate-severe NAFLD (men: OR 1.61, 95% CI 1.24, 2.10 in low 25(OH)D group; OR 3.42, 95% CI 2.41, 4.87 in low SHBG group; women: OR 1.66, 95% CI 1.14, 2.42 in low 25(OH)D group; OR 6.84, 95% CI 4.31, 10.84 in low SHBG group). However, the combined association of low 25(OH)D and low SHBG was much larger, especially in moderate-severe NAFLD (men: OR 6.57, 95% CI 3.87, 11.18; women: OR 8.16, 95% CI 3.98, 16.73). The associations were independent of age, total testosterone, abdominal obesity, diabetes, and lipid profile. The negative associations of 25(OH)D and SHBG levels with NAFLD are strongest when viewed in combination in men and postmenopausal women. Further studies should determine the cause-effect relationship and investigate the underlying mechanisms of this finding.

Association between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in middle age patient with non-alcoholic fatty liver disease.

Background:Liver biopsy is required to diagnose non-alcoholic steatohepatitis in patients with suspected non-alcoholic fatty liver disease (NAFLD). This study aimed to examine the relationship between sonographic diagnosis of fatty liver with histopathologic abnormalities and liver biopsy findings in patient with NAFLD.Materials and Methods:In this cross-sectional study, a total of 180 patients, with an age range of 18-60 year old, with NAFLD based on ultrasonograghic findings were evaluated. Age, sex, body mass index, diabetes mellitus, hypertension, family history of liver disease and laboratory parameters recorded for all patients. Hence, grade of steatosis and stage of fibrosis were evaluated by liver biopsy.Results:A total of 220 patients were enrolled. Liver biopsy was performed in 180 patients. Mean age was 43 ± 10.6 years old and 66% were male. Ultrasonograghic findings showed mild, moderate and severe NAFLD was define in 100 (55.5%), 72 (40%) and 8 (4.5%) of patients, respectively. Liver biopsies showed that steatosis scores of <5%, 5-33% and 33-66% was define in 56 (31%), 116 (64%) and 9 (5%) of patients, respectively. Furthermore, fibrosis was defined as follow; none 92 (51%), mild 68 (38%), moderate 11 (6%), bridging 5 (3%) and cirrhosis 3 (2%) patients. There was no statistically significant relationship between ultrasonograghic findings and steatosis scores (P = 0.44), but statistically significant relationship was found between ultrasonograghic findings and fibrosis stage (P = 0.017).Conclusion:Findings revealed that, in patients with NAFLD, ultrasonographic finding were not in associate to steatosis, but were in relation with fibrosis stage.

Association between nonalcoholic fatty liver disease and coronary artery calcification in postmenopausal women.

Objective:Cardiovascular disease is a leading cause of death in postmenopausal women, and nonalcoholic fatty liver disease (NAFLD) has been known to be associated with cardiovascular disease. However, little information regarding the relationship between NAFLD and coronary artery calcification (CAC) in postmenopausal women is available. The aim of this study was to investigate the association between NAFLD and CAC in postmenopausal women.Methods:Among 4,377 participants who underwent cardiac computed tomography in a health promotion center, 919 postmenopausal women were enrolled. Anthropometric profiles and multiple cardiovascular risk factors were measured. NAFLD was measured by ultrasonography, and CAC was evaluated by cardiac computed tomography. Odds ratios and 95% CI for the presence of CAC, by severity of fatty liver disease, were estimated using logistic regression.Results:Women were stratified into three groups by severity of NAFLD. There were significant differences in cardiovascular parameters among the groups, and prevalence of CAC significantly increased with severity of NAFLD. On logistic regression analysis after adjustment for multiple risk factors, the odds ratios for the prevalence of CAC were as follows (P < 0.05): no NAFLD, 1.0; mild NAFLD, 1.34 (95% CI, 0.92-2.16); moderate to severe NAFLD, 1.83 (95% CI, 1.06-3.16). However, this association was attenuated after adjustment for insulin resistance (P = 0.16).Conclusions:There is a significant correlation between NAFLD and prevalence of CAC, but NAFLD is not an independent factor for coronary atherosclerosis in postmenopausal women.

Association Between the Severity of Nocturnal Hypoxia in Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Damage.

Background:Obstructive sleep apnea (OSA) is a major disease that can cause significant mortality and morbidity. Chronic intermittent hypoxia is a potential causal factor in the progression from fatty liver to nonalcoholic steatohepatitis.Objectives:This study evaluated the association between the degree of liver steatosis and severity of nocturnal hypoxia.Patients and Methods:In this study, between December 2011 and December 2013, patients with ultrasound-diagnosed NAFLD evaluated by standart polysomnography were subsequentally recorded. Patients with alcohol use, viral hepatitis and other chronic liver diseases were excluded. We analyzed polysomnographic parameters, steatosis level and severity of obstructive sleep apnea (OSA) in consideration of body mass index (BMI), biochemical tests and ultrasonographic liver data of 137 subjects. Patients with sleep apnea and AHI scores of < 5, 5 - 14, 15 - 29 and ≥30 are categorized as control, mild, moderate and severe, respectively.Results:One hundred and thirty-seven patients (76 women, 61 men) with a mean age of 55.75 ± 10.13 years who underwent polysomnography were included in the study. Of 118 patients diagnosed with OSA, 19 (16.1%) had mild OSA, 39 (33.1%) moderate OSA and 60 (50.8%) severe OSA. Nineteen cases formed the control group. Apnea/hypopnea index and oxygen desaturation index (ODI) values were significantly higher in moderate and severe non-alcoholic fatty liver disease (NAFLD) compared to the non-NAFLD group. Mean nocturnal SpO2 values were significantly lower in mild NAFLD and severe NAFLD compared to the non-NAFLD group. Lowest O2 saturation (LaSO2) was found low in mild, moderate and severe NAFLD compared to the non-NAFLD group in a statistically significant manner.Conclusions:We assessed polysomnographic parameters of AHI, ODI, LaSO2 and mean nocturnal SpO2 levels, which are especially important in the association between NAFLD and OSAS. We think that it is necessary to be attentive regarding NAFLD development and progression in patients with OSA whose nocturnal hypoxia is severe.

Increased microalbuminuria prevalence among patients with nonalcoholic fatty liver disease

Aim: To determine the prevalence of microalbuminuria, that is an indirect predictor of coronary artery disease, among non-obese and non-diabetic patients with fatty liver disease. Material and method: This retrospective study was carried out on non-obese (body mass index (BMI) < 30) and non-diabetic 290 female and 189 male, totally 479 cases. All subjects underwent liver ultrasonography scanning to determine the presence and stage of fatty liver disease. Results: The subjects were grouped according to the ultrasound findings as follows: 182 (37.9%) cases without any fat accumulation in liver were regarded as control group; and among remaining cases, 124 (25.8%) had mild, 93 (19.4%) had moderate, and 80 (16.7%) had severe fatty liver disease. There was not any statistically significant difference between groups in regards to the age, gender, liver function tests, renal function tests or glomerular filtration rate. However urinary protein/creatinine ratio was statistically significantly higher in severe nonalcoholic fatty liver disease (NAFLD) group than the other three groups. In moderate and severe NAFLD groups, microalbuminuria was statistically significantly more common compared with the control and mild NAFLD groups. Regarding the results of multiple logistic regression analysis, presence of fatty liver disease increased the risk of microalbuminuria for 1.87 times independently from increased BMI and increased HOMA-IR values. Conclusion: We have determined that microalbuminuria is more prevalent among NAFLD cases compared with control cases and microalbuminuria prevalence was increasing with the advanced stages of NAFLD although two main etiologic factors of microalbuminuria, type 2 diabetes, and obesity were excluded.

PANCREATIC STEATOSIS AND ITS ASSOCIATION WITH NONALCOHOLIC FATTY LIVER DISEASE EVALUATED BY ULTRASONOGRAPHY

Introduction: Pancreatic steatosis (PS) is the fatty replacement of pancreatic parenchyma, being often associated with obesity and aging. Similar to this condition in pancreas, any excessive lipidic deposition in the liver tissue are referred to as nonalcoholic fatty liver disease (NAFLD). Objective: The objective of this study was to explore associations between PS and the NAFLD grade, as evaluated by ultrasonography. Methods: This was a cross-sectional study. Diagnosis of the PS and NAFLD was based on ultrasound findings, and 576 ultrasonography exams were evaluated. The chi-square test was used for evaluation of the relationship between PS and NAFLD. Results: A total of 576 individuals were included, 217 (or 37.7%) were male and 359 (or 62.3%) were female. The median age of the patients was 47.04 (11.8) years-old (mean ± standard error). Among them, 243 were diagnosed with PS and 245 were diagnosed with NAFLD according to the trans-abdominal ultrasound findings. There was an association between male sex and PS (P 0.012), and between female sex and NAFLD (P 0.0001). As compared to the normal group, the PS and NAFLD group was characterized by a significantly higher median age. There was also a statistically significant association between the degree of PS and the degree of NAFLD, with the following characteristics: mild PS and mild NAFLD (P 0.0001), moderate PS and moderate and severe NAFLD (P 0.0001) and between severe PS and moderate and severe NAFLD (P 0.0001). Conclusion: Our findings demonstrated that fat accumulation in pancreas is significantly correlated to NAFLD. It was also shown that the ultrasound is very resourceful when it comes evaluation of fat grade.